From the Journals

Mutation in patients with chronic HCV raises risk of liver cancer

 

Key clinical point: An adenine mutation in the MUTYH gene increased the risk of developing liver cancer in patients with chronic HCV.

Major finding: Hepatocellular carcinoma risk with the mutation was significantly higher than in patients with the standard genotype (OR = 9.27, P = .0005).

Study details: Nineteen SNPs in base excision repair genes were examined in 93 patients with chronic hepatitis C.

Disclosures: The study was supported by grants from the Japan Society for Scientific Research. The authors reported they had nothing to disclose.

Source: Sakurada A et al. Free Radic Biol Med. 2018;129:88-96.


 

FROM FREE RADICAL BIOLOGY AND MEDICINE

An adenine mutation in the MUTYH base repair excision gene increased the risk of developing hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV). The mutation was discovered in an analysis of 19 tagging single-nucleotide polymorphism (SNP) variants examined for multiple base repair excision genes (MUTYH, OGG1, and MTH1), according to the results of a retrospective analysis of patient genotypes reported in Free Radical Biology and Medicine (2018;129:88-96).

DNA sequence ©Gio_tto/Thinkstock.com

In addition, the researchers examined MUTYH-null mice to assess the involvement of oxidative stress and DNA repair enzymes in hepatocarcinogenesis.

One significant SNP was found and confirmed from 93 Japanese patients with chronic HCV (38 with HCC and 55 controls), according to Akira Sakurada, MD, of Sapporo (Japan) Medical University, and his colleagues.

Patients diagnosed as having chronic HCV between 2007 and 2015 were enrolled. All patients were 45 years of age or older with detectable anti-HCV antibodies and HCV-RNA, as well as histopathological evidence of chronic hepatitis on liver biopsy. An exploratory cohort of 40 patients was first used before the 93 patient confirmatory analysis.

Genomic DNA was extracted from peripheral mononuclear cells of all of the patients studied.

Dr. Sakurada and his colleagues found significant associations for the single intron SNP (rs3219487) in the MUTYH gene. Human MutY homolog (MUTYH) protein is responsible for recognition and removal of an inappropriately inserted adenine (A).

The risk of developing HCC in patients with A/A or G/A genotypes was higher than in those with the G/G genotype (odds ratio = 9.27, 95% confidence interval = 2.39-32.1, P = .0005). In addition, they found that MUTYH mRNA levels were significantly lower in G/A or A/A genotyped subjects as compared with the wild type (G/G) (P = .0157 and P = .0108, respectively).

In their mouse model, the investigators found that liver tumors developed in MUTYH-null mice. As a physiological confirmation of their results, the researchers investigated a MUTYH-null mouse model. They found that decreased MUTYH activity in the null mice resulted in the development of HCC in these animals after 12 months of a high iron diet, but no tumors were observed when a dietary antioxidant (N-Acetyl-L-cysteine) was also provided.

“HCC may develop even in patients with an SVR [sustained virologic response]. This may be a problem especially for the numerous elderly patients. Our study suggests that SNP genotyping may predict the risk of developing HCC in such patients. We propose that in the setting of appropriate screening intervals, stratification of patients for whom antioxidant treatment would be appropriate could be achieved in this manner,” the researchers concluded.

The study was supported by grants from the Japan Society for Scientific Research. The authors reported they had nothing to disclose.

SOURCE: Sakurada A et al. Free Radic Biol Med. 2018;129:88-96.

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